Relationship between Plasma Levels of Zinc and Clinical Course of Pneumonia.

BACKGROUND
Pneumonia is a common disease and is more prevalent among children and the elderly. Zinc (Zn) is an essential substance for the human body and plays an important role in regulating the immune system. Studies have shown a possible relation between the Zn plasma levels and pneumonia.


MATERIALS AND METHODS
In a cross-sectional study, 100 patients with pneumonia, who were referred to the Educational-Medical Centers of Tabriz University of Medical Sciences, were included in the study. The plasma levels of Zn of all patients were measured. The patients were divided into two groups of normal and low plasma levels of Zn. The severity and clinical course of pneumonia, including the durations of fever, tachycardia, and tachypnea were evaluated and compared between the two groups.


RESULTS
The plasma levels of Zn were normal in 56 patients and low in 44 patients. The mean duration of fever, tachycardia, and tachypnea in the group with normal plasma levels of Zn were 1.58±0.68, 2.04±0.81, and 2.78±0.84 days, respectively; and those in the group with decreased Zn plasma levels were 1.72±0.70, 2.18±0.90, and 2.97±0.91 days, respectively. There were no statistically significant differences between the two groups (P>0.05). However, the incidence of severe pneumonia was significantly less in the group with normal Zn plasma levels (P=0.001).


CONCLUSION
Based on the findings of the present study, there was no statistically significant relationship between the plasma levels of Zn and the clinical course of pneumonia. However, Zn lowered the incidence of severe pneumonia.


INTRODUCTION
Pneumonia is an inflammatory state of the lungs, mainly affecting the alveoli, having diverse causative organisms and mechanisms (1). Pneumonia is one of the most common infectious diseases, affecting 4 to 6 million people in the United States of America in the form of community acquired pneumonia (CAD), more than a million of those affected requiring hospitalization (2,3).
The most common age groups involved are children younger than 5 years of age and elderly aged more than 65 years (4,5). Risk factors for acquiring pneumonia include age more than 60 years, alcoholism, cardiac diseases, immunosuppressive therapies, smoking, history of previous pneumonia, mechanical ventilation, body mass index (BMI) less than 18.5, and diabetes (6)(7)(8)(9)(10). Pneumonia imposes a heavy burden on the health system of nations worldwide with an estimated expenditure of 17 billion dollars in the United States alone (11); this is more disturbing, knowing that the disease is almost 5 times  (14), regulating the immune system, and enhancing the cellular immunity (15), being an essential factor for the optimal functioning of macrophages and lymphocytes (16).
Moreover, it has been shown that Zn could function as an anti-oxidant (17), playing an important role in the course of infectious diseases. It has also been demonstrated that children with low levels of plasma Zn were at a higher risk of acquiring pneumonia (18,19). It has also been suggested that supplementation of Zn in the therapeutic regimen of children with pneumonia could improve the results, and boost the chances of leaving the hospital with no long term complications (20). However, data on the significance of Zn in preventing and treating pneumonia are limited and inconclusive (21). A study found that supplementation of Zn in children with severe pneumonia did not have any significant effect on the duration of the disease (22).
Moreover, Zn plasma levels are confounded by several aspects, including geographical factors, race, sex, and socio-economic status (23)(24)(25), making it harder to generalize the results of these studies to different contexts.
There are also limited studies on the plasma levels of Zn in patients with pneumonia, analyzing the relation between it and the clinical outcome.
The present study sought to further evaluate the effect of plasma levels of Zn on the clinical course of patients with pneumonia, and the relation between the severity of the disease acquired and plasma levels of Zn.

MATERIALS AND METHODS
During the present cross-sectional study, conducted between April 2015 and April 2016, in the Educational-Medical Centers of Tabriz University of Medical Sciences (Tabriz, Iran), these being the main referral centers for infectious diseases in North-Western Iran. A total of 100 patients were included in this study; they were divided into two groups with low (44 patients) and normal (56 patients) plasma zinc levels. The age, sex, and risk factors, such as smoking, occupation, and BMI, were evaluated; the differences between the two groups were not significant. A drug history was obtained from all patients before inclusion in the study. The inclusion criteria were age between 15 and 65 years, and a definite diagnosis of pneumonia on chest radiography, the gold-standard test for the diagnosis of pneumonia (26,27). The exclusion criteria were hemodynamic instability, presence of congenital respiratory defects, history of previous autoimmune diseases, pneumonia caused by medication, chemotherapy, hospitalization during the previous year, and use of Zn supplementation during the two months prior to inclusion in the study. All patients were clearly informed about the steps of the study and written informed consent was obtained from all patients; the patients were treated using the most recent guidelines, and after the disease was cured, they were discharged from the infectious disease ward. The study protocol was approved by the Regional Ethics Committee of Tabriz  between the two groups. The severity of pneumonia was determined using the pneumonia severity index (PSI) or PORT Score (29). Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software version 16.0 (SPSS Inc., Chicago, IL). Quantitative data were presented as mean ± standard deviation (SD) and qualitative data as frequency and percentages (%). For statistical analysis, after determining the distribution of continuous variables using the Klomogorov-Smirnov test, independent sample t-test was used to compare the results between the two groups. Moreover, the collected data were analyzed using descriptive statistical methods, mean difference test for independent groups, and chi-square test or Fisher's exact test. A P-value less than 0.05 was considered statistically significant in all steps.

RESULTS
The mean age was 36.  Table 1. The means of the above-mentioned variables for the two groups and the comparison between them are shown in Table 2. The differences between the two groups regarding the number of days of hospitalization and the number of days with leukocytosis, tachycardia, tachypnea, and fever were not statistically significant (P>0.05). During the present study, no case of mortality was observed, and all patients were discharged from the infectious disease ward; thus, the groups had no significant differences between them.  Regarding the severity of acquired pneumonia as determined by the PSI score, of the total of 100 patients, 28 had severe pneumonia, 26 belonging to the group with low plasma levels of Zn (59%), and the remaining two belonging to the group with normal plasma levels of Zn (3.5%); the difference between the two groups was statistically significant (P=0.001). The data are summarized in Table 1.

DISCUSSION
During the present cross-sectional study, it was found that there was a significant relation between the Zn plasma levels and the severity of the disease acquired (P=0.001).
However, there was no significant relation between the Zn